Two related but distinct G-protein coupled purinergic receptors, P2Y1 and P2Y12, have been shown to exhibit significant reduction in ADP-induced platelet aggregation.  Inhibition of the P2Y12 receptor has resulted in several important marketed antithrombotic agents. Our recent preclinical studies have shown that inhibition of  P2Y1 or P2Y12  provides equivalent antithrombotic efficacy.  However, targeting P2Y1 antagonism has shown the potential benefit of providing a reduced bleeding liability. We have previously disclosed a series of spiropiperidinyl indolinyldiaryl ureas  as small molecule P2Y1 antagonists. This poster describes the further optimization of this series which gave rise to a series of spiropiperidine analogs with improved potency in the platelet aggregation assay. This work culminated in BMS-816106, a novel potent antiplatelet agent. The SAR leading to this compound, synthesis, and in vivo data will be described.

Identification of BMS-816106, potent P2Y<sub>1</sub> antagonist as a novel antiplatelet agent

244th National Meeting (2012)

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Identification of BMS-816106, potent P2Y1 antagonist as a novel antiplatelet agent

Identification of BMS-816106, potent P2Y₁ antagonist as a novel antiplatelet agent